Membrane transport disorders detected in erythrocytes may be markers of widespread defects in cellular ion metabolism. Recent research has characterized two groups with reproducible cation transport abnormalities: lithium-sodium countertransport is accelerated in hypertensives, and sodium-potassium cotransport is depressed in blacks. There is ample reason to presume that countertransport and cotransport systems virtually identical to those in red cells are present in kidney tubules where they effect proximal tubular and thick ascending limb of Henle reabsorptive functions, respectively. We will therefore test the hypothesis that alterations in these red cell cation transport pathways reflect two distinct renal tubular dysfunctions in sodium handling. Countertransport: The erythrocyte lithium-sodium countertransport system shares kinetic characteristics and ion specificities with the proximal tubular sodium-hydrogen exchanger, which is likely the mechanism responsible for proximal lithium reabsorption. In the proximal tubule, lithium reabsorption parallels sodium reabsorption, and since lithium is not affected by post-proximal tubular processes, urinary lithium clearance can be employed as a marker for proximal tubular sodium handling. Lithium clearance studies in hypertensives and normotensives under conditions of sodium balance and during acute sodium loading will test the hypothesis that the accelerated erythrocyte countertransport in human hypertension is associated with heightened proximal renal sodium reabsorption. Cotransport: Sodium-potassium cotransport is another transport mode shared by erythrocytes and renal tubules. In the kidney, cotransport is clearly localized to the thick ascending limb of the loop of Henle, where it is responsible for the generation of free water through net ion reabsorption. Inhibition of cotransport by furosemide is manifested by decreased free water and increased chloride clearances, and responses in these measures will be employed as indices of cotransport activity. The hypothesis that renal responses to furosemide will be related to previously described racial differences in erythrocyte cotransport activity will be tested.